Soluble CD23 Controls IgE Synthesis and Homeostasis in Human B Cells

The present results indicate that B cells isolated from chronic lymphocytic leukemia (B-CLL) from 11 of 14 patients are capable of specifically producing IgE upon costimulation with IL-4 and hydrocortisone (HC). IgE is detected by intracytoplasmic fluorescence staining and by RIA. Clinical, hematological, and immunological parameters (including Rai stage, WBC, Lc, sIg kappa/lambda, CD5, and CD23 expression) cannot distinguish the IgE responder from the nonresponder patients. IL-4 alone is a potent inducer of human IgE synthesis by normal PBMC and we show here that its effect is strikingly enhanced by HC. The IgE produced by B-CLLs are monoclonal since they display the same L chain type as the freshly isolated CD5+ B-CLLs. We, therefore, conclude that the combination of IL-4 and HC can abrogate the maturation arrest of CD5+ B-CLLs by inducing their differentiation into IgE-producing cells. The present data provide a unique model to study the isotype switching to IgE and the regulation of human IgE synthesis by monoclonal human B cells.

Download Full-text

Mechanisms of inhibition of IgE synthesis by nedocromil sodium: Nedocromil sodium inhibits deletional switch recombination in human B cells

Journal of Allergy and Clinical Immunology ◽

10.1016/s0091-6749(96)70269-5 ◽

1996 ◽

Vol 97 (5) ◽

pp. 1141-1150 ◽

Cited By ~ 11

Author(s):

Richard K.S. Loh ◽

Haifa H. Jabara ◽

Raif S. Geha

Keyword(s):

B Cells ◽

Nedocromil Sodium ◽

Human B Cells ◽

Ige Synthesis

Download Full-text

Disodium cromoglycate inhibits S mu-->S epsilon deletional switch recombination and IgE synthesis in human B cells.

Journal of Experimental Medicine ◽

10.1084/jem.180.2.663 ◽

1994 ◽

Vol 180 (2) ◽

pp. 663-671 ◽

Cited By ~ 47

Author(s):

R K Loh ◽

H H Jabara ◽

R S Geha

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Allergic Disease ◽

Interleukin 4 ◽

Pokeweed Mitogen ◽

Disodium Cromoglycate ◽

Isotype Switching ◽

Human B Cells ◽

Ige Synthesis

IgE synthesis requires interleukin 4 (IL-4) and a T-B cell interaction that involves the B cell antigen CD40 and its ligand expressed on activated T cells. IL-4 induces epsilon germline transcription whereas ligation of CD40 results in deletional S mu-->S epsilon switch recombination, expression of mature epsilon transcripts, and IgE synthesis and secretion. We demonstrate that disodium cromoglycate (DSCG), a drug commonly used for the prophylactic treatment of allergic disease, inhibits T cell-driven IgE synthesis by human B cells at concentrations readily achievable in the course of inhaled therapy for asthma. Inhibition of IgE synthesis by DSCG was not the result of drug toxicity because DSCG did not affect the viability of T and B cells or their proliferation to mitogens. DSCG did not interfere with CD40 ligand expression by T cells but clearly targeted the B cells because it inhibited IgE synthesis induced by anti-CD40 and IL-4 in populations of highly purified B cells. DSCG had no effect on the induction of epsilon germline transcripts by IL-4 but strongly inhibited CD40 mediated S mu-->S epsilon deletional switch recombination in IL-4-treated B cells as assayed by nested primer PCR. The effect of DSCG was not specific for CD40-mediated induction of IgE isotype switching because DSCG inhibited IgE synthesis as well as S mu-->S epsilon deletional switch recombination induced by hydrocortisone and IL-4 in B cells. Moreover, the effect of DSCG was not specific for IgE isotype switching because DSCG inhibited the synthesis of IgG4 by B cells sorted for lack of surface expression of IgG4 and stimulated with anti-CD40 and IL-4. DSCG caused only minimal inhibition (< 15%) of spontaneous IgE synthesis by lymphocytes from patients with the hyper-IgE syndrome and did not affect pokeweed mitogen-induced IgG and IgA synthesis by lymphocytes suggesting that it has little effect on B cells that have already undergone isotype switching. These results indicate that DSCG inhibits switching to IgE in B cells and suggest a novel potential mechanism for the prevention of allergic disease by DSCG.

Download Full-text